LONG-TERM GENDER-SPECIFIC EFFECTS OF MANIPULATION DURING PREGNANCY ONIMMUNE AND ENDOCRINE RESPONSIVENESS IN RAT OFFSPRING

Exposure to synthetic glucocorticoids (GCs) or other stimuli around bi rth may affect neuroendocrine and immune responsiveness in the offspri ng. Experiments were conducted to investigate whether maternal manipul ation with saline or with GCs alters the corticosterone (CORT) respons e to a mild stressor in the offspring, and whether maternal manipulati on results in long-term altered in vivo humoral and cellular immune re sponsiveness in the offspring. Pregnant rats were given dexamethasone( DEX, 1.2 mg/kg body weight, i.p.) or saline (SAL) at day 17 and 19 of gestation. A third group of pregnant rats was left undisturbed (UNTR-g roup). After maternal DEX treatment no altered CORT response was seen to a novel environment at 20 days of age. as compared to both the SAL- treated group and the UNTR-group. However, saline administration to pr egnant rah caused an increased CORT response in female offspring, but not malt: offspring, as compared to the UNTR-group (P less than or equ al to 0.01). Furthermore, no effects of maternal DEX exposure were see n on IgG2a production after immunization with a conjugated pneumococca l polysaccharide (PPS-14-CRM197) at 6 weeks of age. However, maternal SAL treatment enhanced anti-PPS-14 IgG2a antibody levels in female off spring, but not ill male offspring, as compared to the UNTR-group (P l ess than or equal to 0.05). Cellular immune responses were measured by an oxazolone-induced contact hypersensitivity response (CHS-response) , at 8 weeks of age. Maternal SAL treatment increased the CHS response in adult male rats, but not in female rats;, as compared to both the UNTR-group and the DEX-group (P less than or equal to 0.005). These da ta suggest that manipulations during late pregnancy not only affect en docrine responsiveness, but also influence immune responsiveness in th e rat offspring. Furthermore, these effects may belong-term and gender -specific. (C) 1998 Elsevier Science B.V.